The existence of an alternate pathway for complement (C) activation has been established and several studies have demonstrated a role for this system in host resistance to infection and in the production of tissue injury. Two systems which function as alternate pathways to the C system have been described. These systems are the properdin system, first described by Pillemer and associates, and the C3 activator system (described by Gotze and Muller-Eberhard) and they probably represent the same alternate pathway for C activation. The mechanism has not been described by which the alternate pathway is activated and the early acting components are unknown. Furthermore, the sequence in which the components act and the mechanism of their action have not been determined. The primary objective of this project is to define the mechanisms which govern the activation of the properdin system. Since the properdin system is activated by zymosan and other polysaccharides, experiments will be performed to determine which serum proteins react with zymosan to form a complex capable of initiating C action through a reaction with C3. The early acting components of the properdin system will be purified by column chromatography, and the sequence and mechanism of their action studied. Properdin is believed to be one of the early acting components of the properdin system and studies of this unique serum protein will be stressed. Native properdin, or properdin which has not reacted to form a complex with zymosan will be purified, labeled with I125 and the mechanism of its uptake by zymosan determined. Properdin which has reacted to form a complex with zymosan will also be purified. The physicochemical and electrophoretic properties of these two properdin preparations will be compared to determine whether properdin is altered during the formation of a complex with zymosan. A possible role for the properdin system in the pathogenesis of certain human diseases also will be investigated.